The aggravatory effect of nicotine on Helicobacter pylori-induced gastric mucosa injury: role of asymmetric dimethylarginine.
OBJECTIVE
Nitric oxide (NO) is a well-known gastric mucosa protection factor. Recently, it has been reported that methylated arginine compound such as asymmetric dimethylarginine (ADMA), which inhibits nitric oxide synthesis, may be related to the development of gastric mucosa injury in patients with Helicobacter pylori infection. In the present study, we tested the relationship between endogenous ADMA and gastric mucosa injury in H. pylor- infected patients and cultured gastric epithelial cells.


METHODS
One hundred and fifty subjects with gastric diseases were entered in this study. The levels of ADMA in gastric juice and plasma were measured in both H. pylori+ and H. pylori- patients. We analyzed independent risk factors that contribute to ADMA levels by multiple linear regression analyses. Mucosal epithelium cells were treated with nicotine (10 microM) for 24 hours in the presence or absence of H. pylori. The concentrations of ADMA in the culture medium and the rate of cell apoptosis were determined.


RESULTS
The ADMA level in gastric juice was significantly increased in H. pylori+ patients (P<0.05), whereas there were no differences in the content of ADMA in the plasma between H. pylori+ patients and H. pylori- patients. Smoking and H. pylori infection were 2 independent risk factors contributing to ADMA levels, and in the population of H. pylori+ patients, the level of ADMA in smokers was higher compared with nonsmokers. Incubation of nicotine (10 microM) with epithelial cells for 24 hours further increased the elevated level of ADMA and the rate of cell apoptosis owing to H. pylori infection.


CONCLUSIONS
H. pylori infection caused an increase of ADMA levels in gastric juice, which was aggravated by smoking. Endogenous ADMA may be an important factor contributing to gastric mucosa injury.
Zhang
Zhe
Z
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Zou
Yi-You
YY
Zhou
Yuan
Y
Zhou
Hui
H
Li
Yuan-Jian
YJ
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005773:Gastroscopy; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects*; D009569:Nitric Oxide / Q000378:metabolism; D013276:Stomach Ulcer / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D055815:Young Adult
C487735:dimethylarginine; D009569:Nitric Oxide; D009538:Nicotine; D001120:Arginine